Poster Presentation 8th Australasian Virology Society Meeting and 11th Annual Meeting of the Australian Centre for Hepatitis & HIV Virology Meeting 2015

Infection of macrophages by seasonal influenza viruses is restricted at the level of virus entry and at late stage in the virus life cycle (#158)

Sarah L Londrigan 1 , Kirsty R Short 1 , Joel Ma , Leah Gillespie , Steven P Rockman 2 , Andrew G Brooks , Patrick C Reading 1 3
  1. Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
  2. bioCSL Limited, Parkville, Vic, Australia
  3. WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia

Airway macrophages (MΦ) are an important component of the innate host-defence against influenza A virus (IAV), initiating local inflammatory responses and priming subsequent adaptive responses. Historically, MΦ have also been considered to play a critical role in controlling the severity of IAV infection by limiting virus release through “abortive infection” such that infectious virus particles are not released from infected cells. In contrast, highly pathogenic H5N1 IAV strains have been reported to replicate productively in MΦ, which may have important consequences in terms of viral amplification and dissemination in an infected individual. We compared mouse MΦ and epithelial cells for their ability to support viral genomic replication and transcription, synthesis of viral proteins, assembly of virions and release of infectious progeny following exposure to genetically defined IAV strains.  We confirmed that seasonal IAV differ in their ability to utilize cell-surface receptors for infectious entry into MΦ and that this represents one level of virus restriction.  Following virus entry, we demonstrated that virus assembly is defective in IAV - infected MΦ, despite synthesis of all 8 segments of genomic viral (v) RNA and messenger (m) RNA and the production of 7 distinct IAV proteins.  This defines a second level of restriction late in the virus life cycle in IAV-infected MΦ where virus assembly is defective and newly synthesized virions are not released.  This study represents an important step in understanding how productive infection of MΦ by seasonal IAV strains is impaired and the extent to which to replication cycle proceeds.  Current studies are focused on (i) identifying cellular factors responsible for limiting productive infection of MΦ by seasonal IAV and (ii) investigating the viral determinants that enable highly pathogenic IAV strains to evade the host MΦ response and replicate productively in these cells.